Topological impact of noncanonical DNA structures on Klenow fragment of DNA polymerase

DOI Web Site 被引用文献22件 参考文献46件 オープンアクセス
  • Shuntaro Takahashi
    Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20 Minatojima-minamimachi, Kobe 650-0047, Japan;
  • John A. Brazier
    Department of Pharmacy, University of Reading, Whiteknights, Reading, Berkshire RG6 6AD, United Kingdom;
  • Naoki Sugimoto
    Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20 Minatojima-minamimachi, Kobe 650-0047, Japan;

説明

<jats:title>Significance</jats:title> <jats:p>Alterations in nonduplex structures could play roles during DNA replication in the progression of cancer and other intractable diseases. These noncanonical structures differ topologically from each other. However, the role of these differences in diseases remains unknown. In this study, we found that the presence of i-motif structures in the template caused the DNA polymerase to stall immediately before these structures. The i-motif structures are more efficient than other structures, such as G-quadruplexes and hairpins, although their thermodynamic stabilities are similar. This inhibition effect of the DNA polymerase was regulated by molecular crowding, which mimics conditions in the cell. Therefore, it is possible that the i-motif could impede DNA replication or repair and cause genomic instability.</jats:p>

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